Modulation of mucus production by interleukin-13 receptor alpha2 in the human airway epithelium

Clin Exp Allergy. 2008 Jan;38(1):122-34. doi: 10.1111/j.1365-2222.2007.02871.x. Epub 2007 Nov 19.

Abstract

Background: IL-13 induces goblet cell hyperplasia and mucus overproduction in airway epithelial cells. IL-13 receptor alpha2 (IL-13Ralpha(2)) has been suggested to act as a 'decoy receptor' in the airway epithelium by inhibiting the IL-13 signal. However, the regulatory mechanisms for mucus production by IL-13Ralpha(2) remain unclear.

Objective: The aim of this study was to examine the role of IL-13Ralpha(2) in goblet cell hyperplasia and mucus overproduction by IL-13.

Methods: Bronchi were obtained from patients who underwent a lung resection due to lung cancer or benign lung tumours. Normal human bronchial epithelial cells (NHBECs) were isolated and cultured using an air-liquid interface (ALI) method.

Results: The number of periodic acid-Schiff's (PAS)-positive cells, goblet cells and MUC5AC-positive cells increased after adding IL-13 into NHBECs. The concentrations of MUC5AC protein in the supernatant and the mRNA expression of MUC5AC significantly increased after adding IL-13, and returned to control levels at 21 days. The mRNA expression of IL-13Ralpha(2) significantly increased at 7 days and then continuously increased up to 21 days. The protein of a soluble form of IL-13Ralpha(2) in the supernatants significantly increased at 14 and 21 days. Anti-IL-13Ralpha(1) antibody and recombinant IL-13Ralpha(2) reduced the number of PAS-positive cells, goblet cells and MUC5AC-positive cells, and MUC5AC mRNA, while the anti-IL-13Ralpha(2) antibody increased the number of these cells and MUC5AC mRNA. The concentration of MUC5AC protein in the supernatant induced by IL-13 was reduced by anti- IL-13Ralpha(1) antibody and recombinant IL-13Ralpha(2). IL-13-induced signal transducer and activator of transcription (STAT) activation was inhibited by anti-IL-13Ralpha(1) antibody and recombinant IL-13Ralpha(2). In contrast, the IL-4-induced mucus production, mucus secretion and STAT activation were not inhibited by recombinant IL-13Ralpha(2).

Conclusion: The soluble form of IL-13Ralpha(2) may therefore modulate mucus overproduction by IL-13 through the pathway including IL-13Ralpha(1) in NHBECs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies / immunology
  • Cells, Cultured
  • Epithelium / drug effects
  • Epithelium / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Hyperplasia / chemically induced
  • Interleukin-13 / pharmacology
  • Interleukin-13 Receptor alpha2 Subunit / genetics
  • Interleukin-13 Receptor alpha2 Subunit / immunology
  • Interleukin-13 Receptor alpha2 Subunit / metabolism*
  • Lung / drug effects
  • Lung / metabolism*
  • Middle Aged
  • Mucin 5AC
  • Mucins / metabolism
  • Mucus / drug effects
  • Mucus / immunology
  • Mucus / metabolism*
  • RNA, Messenger / genetics
  • Signal Transduction
  • Solubility
  • Time Factors
  • Transcription, Genetic / genetics

Substances

  • Antibodies
  • Interleukin-13
  • Interleukin-13 Receptor alpha2 Subunit
  • MUC5AC protein, human
  • Mucin 5AC
  • Mucins
  • RNA, Messenger